The release of chemicals such as chlorinated solvents, pesticides and other xenobiotic organic compounds to streams, either from contaminated sites, accidental or direct application/release, is a significant threat to water resources. In this paper, different methods for evaluating the impacts of chemical stressors on stream ecosystems are evaluated for a stream in Denmark where the effects of major physical habitat degradation can be disregarded. The methods are: (i) the Danish Stream Fauna Index, (ii) Toxic Units (TU), (iii) SPEAR indices, (iv) Hazard Quotient (HQ) index and (v) AQUATOX, an ecological model. The results showed that the hydromorphology, nutrients, biological oxygen demand and contaminants (pesticides and trichloroethylene from a contaminated site) originating from groundwater do not affect the good ecological status in the stream. In contrast, the evaluation by the novel SPEAR(pesticides) index and TU indicated that the site is far from obtaining good ecological status - a direct contradiction to the ecological index currently in use in Denmark today - most likely due to stream sediment-bound pesticides arising from the spring spraying season. In order to generalise the findings of this case study, the HQ index and AQUATOX were extended for additional compounds, not only partly to identify potential compounds of concern, but also to determine thresholds where ecological impacts could be expected to occur. The results demonstrate that some commonly used methods for the assessment of ecological impact are not sufficient for capturing - and ideally separating - the effects of all anthropogenic stressors affecting ecosystems. Predictive modelling techniques can be especially useful in supporting early decisions on prioritising hot spots, serving to identify knowledge gaps and thereby direct future data collection. This case study presents a strong argument for combining bioassessment and modelling techniques to multi-stressor field sites, especially before cost-intensive studies are conducted.